The presumed cause of AIDS is a retrovirus, HIV, the human immunodeficiency virus which infects lymphocytes and can be isolated from the blood of AIDS patients (1-3). However, only a small percentage of people infected with this virus have developed the full AIDS syndrome (4). Thus, a cofactor that enhances infection or disease expression by this virus is a possibility. Cytomegalovirus (CMV) is a logical cofactor candidate since nearly all adult AIDS cases are seropositive for CMV (5) and CMV infection causes immune dysfunction (6). In order to shed light on the possible role of CMV as a cofactor in the pathogenesis of AIDS, the studies will examine, in vitro, whether there are synergistic interelationships between these two viruses. Using peripheral blood mononuclear cells (PBMC) and cell lines our specific goals are to determine whether 1) HIV superinfection of cells pre-infected with CMV enhances HIV replication as compared to cells not preinfected with CMV; 2) CMV superinfection of HIV pre-infected cells enhances replication of HIV; 3) HIV superinfection of cells latently infected with CMV lead to reactivation and productive replication of CMV; 4) CMV superinfection of HIV infected cells enhances CMV replication.